Modification of tumor cells by a low dose of Newcastle disease virus. III. Potentiation of tumor-specific cytolytic T cell activity via induction of interferon-alpha/beta.
To investigate possibilities of augmenting tumor-specific immune responses against the highly metastatic murine lymphoma ESb, we tested the effects of the interferon inducer newcastle disease virus (NDV) or of interferon-alpha/beta as costimulator in mixed lymphocyte-tumor cell cultures (MLTC) on the tumor-specific cytolytic T cell (CTL) response. Both approaches, namely stimulation of ESb immune spleen cells with NDV-modified stimulator cells or with ESb stimulator cells and exogenous IFN-alpha/beta, led to a selective potentiation of tumor-specific CTL activity. The potent activation of tumor-specific CTL precursor (CTLP) required the simultaneous presence of the specific ESb tumor antigen--possibly to mediate a signal via the corresponding T cell receptor--and costimulators--possibly to mediate second activation signals. Increased CTL activity required only very low amounts of NDV or IFN-alpha/beta. The generation of CTL activity in the MLTC cultures could be blocked by antisera to IFN-alpha/beta, not, however by control sera. Similar effects were observed in vivo, suggesting that IFN-alpha/beta not only caused an increase in CTL activity, but was essential for the generation of CTL activity. The reduction of the generation of CTL by antiserum to IFN-alpha/beta could be overcome by excess interferon, especially when using ESb-NDV as stimulator cells.
von Hoegen
P
P
Institut für Immunologie und Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
Zawatzky
R
R
Schirrmacher
V
V
D000818:Animals; D005260:Female; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D007370:Interferon Type I / Q000096:biosynthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D009522:Newcastle disease virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007106:Immune Sera; D007370:Interferon Type I